THU0182 THE EFFECTIVENESS OF BIOLOGICAL AGENTS CONCOMITANT WITH TACROLIMUS IN RHEUMATOID ARTHRITIS
Authors: K. Terabe, N. Takahashi, S. Asai, A. Kaneko, Y. Hirano, Y. Kanayama, Y. Yabe, T. Kojima, N. Ishiguro
Journal: Annals of the Rheumatic Diseases (2020)

Background: In Japan, oral tacrolimus (TAC) was approved for the treatment of RA in 2005 and the improvement of symptoms thorough the use concomitant with disease modifying antirheumatic drugs (DMARDs), including MTX has been reported 1 2 . On the other hand, the efficacy and tolerance of biological agents therapy concomitant with TAC are unknown. Objectives: The objective of this study was to investigate the efficacy and tolerance of biological agents concomitant with TAC in Japanese patients with RA using retention rate analysis. Methods: Total patients (n=2860) who underwent 5 biological agents (etanercept: ETN, adalimumab: ADA, golimumab:GLM, tocilizumab: TCZ, abatacept: ABT) treatment between 2003 and 2017 at Nagoya University Hospital and 12 other institutes (Tsurumai Biologics Communication Study Group) were enrolled 3 . In each biologics analysis, patients were divided into three groups: (1) concomitant only MTX (MTX group) (2) concomitant only TAC (TAC group) (3) others (others group). In TAC or MTX group, these drugs were only ones which concomitant with biologics. Kaplan-Meier analysis was used to estimate retention rate in each biologics group. To estimate the tolerance of concomitant biologics with TAC, cumulative hazard function in adverse events rate was performed in each biologics group. In both analyses, hazard ratios (HR) were assessed by Cox proportional hazards modeling adjusted for age, sex, disease duration and previously used biologics. Results: In total 2860 patients, 142 patients (5.0%) administered each biologics concomitant with TAC (ETN: n=47, ADA: n=10 GLM: n=14, TCZ: n=27, ABT: n=49). Baseline characteristics of 142 patients were shown in table 1. Average dosages of TAC at starting were ETN: 2.2±0.7mg ADA: 2.4±1.0mg GLM: 1.9±1.0mg TCZ: 1.7±0.9mg ABT: 1.9±0.9mg. With comparison of retention rate between 3 groups in each biologics under analysis of cox proportional hazard modeling, in ETN and ABT analysis, the retention rate of TAC group was higher than others group (table 2, figure 1). Comparison of incidence of adverse event between 3 group using cumulative hazard function and cox proportional hazard modeling in ETN and ABT analysis. In ETN analysis, incident rate of other group was higher than TAC group. In ABT analysis, there was no significant difference between 3 gruops (figure 2). Table 1. Baseline characteristic (n=142 ) age (years) 63 ± 3 gender male 33 (23%) female 109 (77%) disease duration (years) 12.0 ± 7.8 stage 1,2 34 (24%) 3,4 108 (76%) class 1,2 99 (70%) 3,4 43 (30%) naïve vs switch naïve 71 (50%) switch 71 (50%) corticosteroid use, no (%) + 98 (75%) - 32 (25%) corticosteroid dose (mg) 5.6 ± 3.2 DAS28-ESR 4.71 ± 1.55 Table 2. HR (95%CI)/p-value n (MTX/TAC/others) ETN ADA GLM TCZ ABT (774/ 47/ 486) (339/ 10/ 135) (156/ 14/ 61) (272/ 27/ 207) (213/ 49/ 178) TAC vs others 0.27 (0.16-0.45 ) &lt;0.001 0.9 (0.37-2.20) ns 0.46 (0.13-1.63) ns 0.55 (0.24-1.31) ns 0.51 (0.26-0.97 ) &lt;0.05 TAC vs MTX 0.65 (0.38-1.08) ns 1.42 (0.61-3.31) ns 0.83 (0.24-2.87) ns 0.5 (0.21-1.17) ns 0.74 (0.39-1.42) ns MTX vs others 0.42 (0.35-0.50 ) &lt;0.001 0.9 (0.50-0.88 ) &lt;0.001 0.56 (0.33-0.96 ) &lt;0.05 1.01 (0.78-1.57) ns 0.68 (0.46-0.99 ) &lt;0.05 Bold italic: p&lt;0.05 CI: confidence interval ns: not significant Conclusion: We suspected that, in ETN and ABT treatment, combination therapy with TAC are subsequent options for treatment to RA patients, especially in whom MTX cannot be administration. References: [1]Kino T, et al. Antibiot. 1987 Sep 40(9): 1256-65 [2]Kondo H, et al. J Rheumatol. 2004 Feb;31(2):243-51 [3]Kojima T, et al. Mod Rheumatol. 2011 Sep 3. Disclosure of Interests: KENYA TERABE: None declared, Nobunori Takahashi Speakers bureau: AbbVie, Asahi Kasei, Astellas, Bristol-Myers Squibb, Chugai, Daiichi-Sankyo, Eisai, Eli Lilly, Janssen, Mitsubishi Tanabe, Ono, Pfizer, Takeda, and UCB Japan, Shuji Asai Speakers bureau: AbbVie, Astellas, Bristol-Myers Squibb, Chugai, Daiichi-Sankyo, Eisai, Janssen, Takeda, and UCB Japan, Atsushi Kaneko Speakers bureau: Abbvie, Asahi-Kasei, Astellas, Bristol-Myers Squibb, Chugai, Eisai, Eli Lily, Mitsubishi-Tanabe, Pfizer, and UCB Japan, Yuji Hirano Speakers bureau: Tanabe-Mitsubishi, Pfizer, Eisai, Abbie, Chugai, Bristol-Meyers, Jansen, Astellas, UCB, Eli-Lilly, Asahikasei, Daiichi-Sankyo, Amgen, Yasuhide Kanayama: None declared, Yuichiro Yabe Speakers bureau: Asahi Kasei, Janssen, and Mitsubishi Tanabe, Toshihisa Kojima Grant/research support from: Chugai, Eli Lilly, Astellas, Abbvie, and Novartis, Consultant of: AbbVie, Speakers bureau: AbbVie, Astellas, Bristol-Myers Squibb, Chugai, Daiichi-Sankyo, Eli Lilly, Janssen, Mitsubishi Tanabe, Pfizer, and Takeda, Naoki Ishiguro Grant/research support from: AbbVie, Asahi Kasei, Astellas, Chugai, Daiichi-Sankyo, Eisai, Kaken, Mitsubishi Tanabe, Otsuka, Pfizer, Takeda, and Zimmer Biomet, Consultant of: Ono, Speakers bureau: Astellas, Bristol-Myers Squibb, Daiichi-Sankyo, Eli Lilly, Pfizer, and Taisho Toyama